Differences in locomotor behavior revealed in mice deficient for the calcium-binding proteins parvalbumin, calbindin D-28k or both

Abstract

We investigated the role of the two calcium-binding proteins parvalbumin (PV) and calbindin D-28k (CB) in the locomotor activity and motor coordination using null-mutant mice for PV (PV−/−), CB (CB−/−) or both proteins (PV−/−CB−/−). These proteins are expressed in distinct, mainly non-overlapping populations of neurons of the central and peripheral nervous system and PV additionally in fast-twitch muscles. In a test measuring repeated locomotor activity during 18-20 days, the analysis revealed a slightly increased activity in mice lacking either protein, while the lack of both decreased the number of beams crossed during active periods. An increase in the characteristic speed during the first 8 days could be attributed to PVdeficiency, while the elimination of CB in CB−/− and double-KO mice decreased the percentage of fast movements at all time points. In the latter, additionally a reduction of the fastest speed was observed. The alterations in locomotor activity (fast movements, fastest speed) strongly correlate with the impairment in locomotor coordination in mice deficient for CB evidenced in the runway assay and the rotarod assay. The graded locomotor phenotype (CB > PV) is qualitatively correlated with alterations in Purkinje cell firing reported previously in these mice. The presence or absence of either protein did not affect the spontaneous locomotor activity when animals were placed in a novel environment and tested only once for 30 min. In summary, the lack of these calcium-binding proteins yields characteristic, yet distinct phenotypes with respect to locomotor activity and coordination.

Visual thalamocortical circuits in parvalbumin-deficient mice

“…A decrease in the expression of PV is associated with epileptic seizure susceptibility (Marco et al, 1997;Schwaller et al, 2004), mild behavioral and motor alterations (Farré-Castany et al, 2007), schizophrenia (Pinault, 2011;Lewis et al, 2012), bipolar disorder (Berridge, 2013) and autism spectrum disorder (Oblak et al, 2011). In particular, a reduction in the density of parvalbumin-positive neurons, and schizophrenic traits have recently been demonstrated in the methyl azoxymethanol acetate model of schizophrenia (Lodge et al, 2009).…”

“…The acceleration of the early phase of [Ca 2+ ] i decay associated to PV activity limits or slows down the buildup of residual [Ca 2+ ] i in presynaptic terminals, thus affecting short-term plasticity (Caillard et al, 2000;Vreugdenhil et al, 2003). Several observations indicate that a decrease in the expression of PV is likely to lead to behavioral and neurochemical alterations that have been associated to epileptic seizure susceptibility (Marco et al, 1997;Schwaller et al, 2004;Farré-Castany et al, 2007), schizophrenia (Pinault, 2011;Lewis et al, 2012) and autism spectrum disorder (Oblak et al, 2011). The hypothesis is that elimination of PV produces alterations of brain development during specific periods of pre or postnatal life (Heizmann and Braun, 1992).…”

The effect of parvalbumin deficiency on the acoustic startle response and prepulse inhibition in mice

“…The results obtained in in vitro studies using PV−/− mice suggest that PV has evolved as a functionally distinct, physiologically relevant modulator of intracellular Ca 2+ transients [22,24,25]. Behavioral tests performed in PV−/− mice revealed subtle alterations of locomotor function in comparison with PV+/+ mice, characterized by a slightly increased motor activity, decreased exploratory activity and increased microlinearity of movements [7]. However, the functional consequences of PV deficiency in terms of auditory perception have not been studied until now.…”

Cytosolic Ca2+ Buffers

“…At first glance, these mice show no phenotype related to development, the general morphology of the nervous system, the visual (Wassle et al 1998) and auditory (Airaksinen et al 2000) systems, or behavior under standard housing conditions (Airaksinen et al 1997). CB-D28k 2/2 mice show a mildhowever more severe than PV 2/2 mice-impairment in motor coordination/motor learning (Airaksinen et al 1997;Farre-Castany et al 2007), likely resulting from the 160-Hz oscillations in the cerebellum (Cheron et al 2004;Servais et al 2005). The motor coordination phenotype is due to CB-D28k's absence in Purkinje cells, since this phenotype and alterations in Purkinje cell physiology also occur in mice with Purkinje cell-specific Calb1 ablation (Barski et al 2003).…”

“…Also, PV 2/2 Purkinje cellfiring properties are different from WT ones: The complex spike duration and the spike pause are decreased, and the simple spike-firing rate is increased. These differences in firing properties, together with the oscillations, are the likely cause for the mild locomotor phenotype, that is, a slight impairment of motor coordination/motor learning (Farre-Castany et al 2007).…”